Pathology Commons^™

Recurrent Focal Segmental Glomeruloscleosis Progressing To Collapsing Glomerulopathy In Renal Graft Of An Autopsy Study, C Thorburn, K J Jabbar, W Li, H Kanaan, P Zhang

Conference Presentation Abstracts

Introduction/Objective: Collapsing glomerulopathy (CGN) mainly occurs in patients of African descent because a majority of these patients have APOL-1 gene mutations that results in damage of terminally differentiated podocytes, diffuse fusion of foot processes, and podocyte hyperplasia. Idiopathic FSGS is associated with high rates of recurrent FSGS in renal transplants and can be seen in patients with APOL-1 gene mutations as well, but recurrent FSGS progressing to CGN is not reported. Here we report an autopsy case with renal transplant showing recurrent FSGS progressing to CGN. Methods/Case Report: Our patient was a 32 year old African American man who had …

Gata3 Is A Useful Immunohistochemical Marker To Differentiate Variants Of Renal Tubular Lesions From Different Segments Of Renal Tubules, M Deebajah, Z Qu, P Zhang

Conference Presentation Abstracts

Introduction/Objective GATA3 is found in glomerular mesangial cells, and the distal tubules & collecting ducts in metanephros and eventual kidneys, but not associated with the proximal tubules and loops of Henle. We hypothesize that GATA3 can be used as a marker to identify the origin of tubular differentiation in most renal tumors.

Methods/Case Report Ten negative controls and 43 renal mass lesions (RCC, papillary, clear cell papillary, and chromophobe carcinomas, oncocytoma, and polycystic kidney disease). GATA3 nuclear stain was graded as negative (absent stain), equivocal and positive (< 5 and > 5% cells, respectively). Details of their GATA3 nuclear expression was analyzed for …

Increased Activated Plasma Cells In Inflammatory Bowel Disease When Compared To Ischemic Acute Colitis, C Thornburn, Z Qu, P Zhang

Conference Presentation Abstracts

Introduction/Objective Inflammatory bowel disease (IBD) and acute ischemic colitis can both be involved by active colitis. IBD is characterized by crypt architectural distortion, basal lymphoplasmacytosis, and occasional granulomatous changes. However, diagnosis of IBDs is still largely by exclusion of other types of active colitis with similar changes. We previously demonstrated that glucose regulated protein 94 (grp94) is mainly expressed by activated plasma cells. We postulate that increased numbers of grp94-positive plasma cells may support diagnosis of IBDs. Here, we compared IBD and active ischemic colitis for grp94 expression in mucosal plasma cells of colectomy specimens

Methods/Case Report Tissue sections from …

Case Report. Cryoglobulin Hyaline-Thrombi Associated Acute Jejunitis In A Patient With Type 2 Cryoglobulinemic Glomerulonephritis, Y Al-Othman, Z Qu, P Zhang

Conference Presentation Abstracts

Introduction/Objective Only one prior case report indicates that mixed positive cryoglobulin in serum can be associated with intestinal vasculitis (Annals of Internal Medicine, 1974).

Methods/Case Report We report a 63-year old man with history of positive serum cryoglobulin and hepatitis-C 4 years ago and membranoproliferative pattern of glomerulonephritis with possible cryoglobulin type of deposits by electron microscopy on renal biopsy. After treatment, his hepatitis C became negative. But he was recently found to have monoclonal IgM-kappa and positive cryoglobulin in his serum, and the concurrent renal biopsy showed membranoproliferative pattern of glomerulopathy with many hyaline-thrombi (eosinophilic vascular occlusions with no …

A Case Report Of Autopsy: Large Mass Of Pulmonary Metastatic Calcification In A Patient With End-Stage Renal Disease, V D. Mahalingam, P Zhang

Conference Presentation Abstracts

Introduction/Objective: Metastatic calcifications are reported in patients with end-stage renal disease (ESRD) in radiology literature but there are no pathologic reports regarding this clinical scenario in autopsy. Methods/Case Report: We report the case of a 27-yearold African American man with nephrotoxic injury secondary to gentamicin treatment at a young age leading to ESRD requiring dialysis who then later developed congestive heart disease and arrhythmia. Prior to the patient’s last hospitalization, he had normal breath sounds with no signs of respiratory distress, rales, or wheezing. Imaging of the chest showed a patchy density in the right lung and a large parenchymal …

Role Of Gut Microbiome In Covid-19: An Insight Into Pathogenesis And Therapeutic Potential, Ikram Hussain, Gabriel Liu Yuan Cher, Muhammad Abbas Abid, Muhammad Bilal Abid

Department of Pathology and Laboratory Medicine

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut-lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a "leaky gut". The intestinal permeability then allows access to …

Relationship Between Estimated Average Glucose (Eag) And Fasting Plasma Glucose In A Cohort Of Pakistani Diabetic Subjects, Nanik Ram, Sibtain Ahmed, Saadia Sattar, Saira Furqan, Najmul Islam

Section of Diabetes, Endocrinology and Metabolism

Introduction: Scientific literature is scarce on the utility of estimated average glucose (eAG) from Pakistan. Hence, there is a dire need to evaluate the relationship between eAG and fasting plasma glucose (FPG), in order to enhance our understanding of eAG and its usefulness. This study aims to investigate the relationship between FPG and eAG in diabetic patients calculated using HbA1C.
Materials and methods: A retrospective study was conducted at the Aga Khan University, Karachi, Pakistan. The medical records of both genders in the age range of 18-60 years, presenting as outpatients at the endocrine clinic, labeled as DM, were reviewed …

Impact Of Covid-19 On The Pre And Post Analytical Clinical Laboratory Testing Processes- A Performance Evaluation Study Using Six Sigma, Sibtain Ahmed, Farhat Jahan, Muhammad Umer Naeem Effendi, Farooq Ghani

Department of Pathology and Laboratory Medicine

Background: The aim of this study was to determine the impact of COVID-19 pandemic on the total testing process using six sigma metrics based on a comparison of pre and during pandemic periods.
Material & methods: The study duration was over 12 months, 6 months before and 6 months after the COVID-19 onset in Pakistan in March 2020 after the recognition of the first case, using quality indicators (QIs). QIs were chosen from a model of QIs recommended by the CAP. Analysis was performed using Six Sigma calculators and QIs were expressed in percentage (%) and Sigma value were computed. …

Utilization Of 2d Barcode Technology To Create Surgical Pathology Reports, Zhenhong Qu, Elaine Qu, James Huang, Mark A. Micale, E Li

Conference Presentation Abstracts

Introduction/Objective: After professional transcription service is eliminated, pathologists inevitably undertake the task of diagnostic data entry into pathology repot by adapting a variety of methods such as speech recognition, manual typing, and pre-texted command. Errors and inefficiency in reporting remain common problems, especially for information with unusual syntax such as genotype or nucleotide sequences. To overcome these shortcomings, we introduce here a novel application of a well-established technology as a complementary method, namely 2- dimensional (2D) barcode symbology. Methods/Case Report: Commonly used diagnostic wordings of pathology reports including specimen type, surgical procedure, diagnosis, and test results are collated and organized …

A Unique Case Of Renal Pelvic Urothelial Carcinoma With Extensive Small Round Cell Sarcoma Differentiation Showing Swsr1 Gene Rearrangement, Zubin Shetty, Mitual Amin, Savitha Balaraman, Sugandh Shetty

Conference Presentation Abstracts

Introduction: Ewings-like sarcoma is a rare subgroup of small round cell sarcoma with immunohistochemistry and morphological similarities to Ewing Sarcoma. We report a rare case of renal pelvis invasive urothelial carcinoma with small round cell sarcoma differentiation showing EWSR1 gene rearrangement. Case: An 84-year-old male presented with 6 months of intermittent painless gross hematuria. Workup revealed a 5.4cm left renal pelvicalyceal mass suspicious for transitional cell carcinoma and a 2.5cm enhancing left renal cortical lesion. The patient underwent an uncomplicated robotic left nephroureterectomy. Pathology revealed small round cell sarcoma composing greater than 80% of the renal pelvis tumor with the …

Interobserver Variability In Differentiated Vulvar Intraepithelial Neoplasia Between Surgical Pathology Subspecialties, Grace Y. Wang

Conference Presentation Abstracts

Abstract:Background: Differentiated vulvar intraepithelial neoplasia (dVIN) is a human papillomavirus-independent lesion with potential for rapid progression to invasive squamous cell carcinoma (SCC). The histologic features of dVIN are diverse and have overlapping characteristics with lichen sclerosus (LS) and lichen simplex chronicus (LSC); and may be diagnosed by dermatopathologists or gynecologic pathologists. The goal of our study is to examine interobserver variability in the diagnosis of dVIN between pathologists with different subspecialty expertise. Design: Biopsies diagnosed as dVIN, LS and LSC from 2011-2018 were retrieved from the pathology database at a large academic institution. Using Fleiss kappa statistic, histologic features and …

High-Throughput Next-Generation Sequencing Respiratory Viral Panel: A Diagnostic And Epidemiologic Tool For Sars-Cov-2 And Other Viruses, Nikhil S. Sahajpal, Ashis K. Mondal, Allan Njau, Zachary Petty, Jiani Chen, Sudha Ananth, Pankaj Ahluwalia, Colin Williams, Ted M. Ross, Alka Chaubey

Pathology, East Africa

Two serious public health challenges have emerged in the current COVID-19 pandemic namely, deficits in SARS-CoV-2 variant monitoring and neglect of other co-circulating respiratory viruses. Additionally, accurate assessment of the evolution, extent, and dynamics of the outbreak is required to understand the transmission of the virus. To address these challenges, we evaluated 533 samples using a high-throughput next-generation sequencing (NGS) respiratory viral panel (RVP) that includes 40 viral pathogens. The performance metrics revealed a PPA, NPA, and accuracy of 95.98%, 85.96%, and 94.4%, respectively. The clade for pangolin lineage B that contains certain distant variants, including P4715L in ORF1ab, Q57H …

Labrad : Vol 46, Issue 4 - October 2021, Aga Khan University Hospital, Karachi

LABRAD - Departments of Pathology & Laboratory Medicine and Radiology Archives

• Role of Barcoding in a Clinical Laboratory to Reduce Pre-Analytical Errors
• Congenital Dyserythropoietic Anemia: The Morphological Diagnosis
• Digital Imaging in Hematology: A New Beginning
• Metabolomics: Identification of Fatty Acid Oxidation (FAO) Disorders
• Next-Generation Sequencing for HLA Genotyping
• Urine Metabolomics to identify Organic Academia
• Next-Generation Sequencing (NGS) of Solid Tumor
• Importance of using Genomic Tool in Microbial Identification
• Radiology Practice in 21st Century: Role of Artificial Intelligence
• Case Quiz
• Best of the Recent Past
• Polaroid

Anti-Nmda-Receptor Encephalitis In A Patient With Ovarian Teratoma, Harboring Brain Histology Of Varying Developmental Stages And Regions With Chronic Inflammation, S Fatemi, E Qu, J Fullmer

Conference Presentation Abstracts

Introduction/Objective Anti-NMDA-receptor encephalitis is a subacute, autoimmune disorder thought to be caused by autoantibodies directed against the N-methyl-D-aspartate (NMDA) receptor. Clinical symptoms of anti-NMDAR encephalitis may mimic schizophrenia and psychotic spectrum disorders or substance-induced psychosis. Although initially described in association with ovarian teratomas in women, anti-NMDAR encephalitis has been reported in individuals without paraneoplastic association, as well as in males. Herein, we report a case of a 29-year-old woman with suicidal ideation and other neuropsychiatric manifestations who was found to have a right ovarian cystic mass by imaging study. Microscopically, the resected ovarian mass is composed of mature skin, fat, …

Association Of Body Composition With Odds Of Breast Cancer By Molecular Subtype: Analysis Of The Mechanisms For Established And Novel Risk Factors For Breast Cancer In Nigerian Women (Mend) Study, Tomi Akinyemiju, Kelley Jones, Anjali Gupta, Taofik Oyekunle, Veeral Saraiya, April Deveaux, Omolola Salako, Allison Hall, Olusegun Alatise, Gabriel Ogun, Adewale Adeniyi, Omobolaji Ayandipo, Thomas Olajide, Olalekan Olasehinde, Olukayode Arowolo, Adewale Adisa, Oludolapo Afuwape, Aralola Olusanya, Aderemi Adegoke, Trygve O. Tollefsbol, Donna K. Arnett, H3 Africa Kidney Research Network, Adetola Daramola

Epidemiology and Environmental Health Faculty Publications

BACKGROUND: The association between obesity and breast cancer (BC) has been extensively studied among US, European and Asian study populations, with often conflicting evidence. However, despite the increasing prevalence of obesity and associated conditions in Africa, the continent with the highest age-standardized BC mortality rate globally, few studies have evaluated this association, and none has examined in relation to molecular subtypes among African women. The current analysis examines the association between body composition, defined by body mass index (BMI), height, and weight, and BC by molecular subtype among African women.

METHODS: We estimated odds ratios (ORs) and 95% confidence intervals …

A Case Report Of Metastatic Castration-Resistant Prostate Cancer Harboring A Pten Loss, Zin W. Myint, Derek B. Allison, Carleton S. Ellis

Internal Medicine Faculty Publications

The treatment landscape of metastatic castration-resistant prostate cancer (mCRPC) has dramatically improved over the last decade; however, patients with visceral metastases are still faced with poor outcomes. Phosphatase and tensin homolog (PTEN) loss is observed in 40%–60% of mCRPC patients and is also associated with a poor prognosis. Several PI3K/AKT/mTOR pathway inhibitors have been studied, with disappointing anti-tumor activity. Here, we present a case of a patient with heavily treated mCRPC who had a modest tumor response to concurrent carboplatin, abiraterone acetate/prednisone, and liver-directed radiation therapy. We discuss the potential rationale supporting the use of this combination therapy …

Super-Enhancer-Based Identification Of A Batf3/Il-2r-Module Reveals Vulnerabilities In Anaplastic Large Cell Lymphoma, Huan-Chang Liang, Mariantonia Costanza, Nicole Prutsch, Mark W. Zimmerman, Elisabeth Gurnhofer, Ivonne A. Montes-Mojarro, Brian J. Abraham, Nina Prokoph, Stefan Stoiber, Shahid Pervez

Department of Pathology and Laboratory Medicine

Anaplastic large cell lymphoma (ALCL), an aggressive CD30-positive T-cell lymphoma, comprises systemic anaplastic lymphoma kinase (ALK)-positive, and ALK-negative, primary cutaneous and breast implant-associated ALCL. Prognosis of some ALCL subgroups is still unsatisfactory, and already in second line effective treatment options are lacking. To identify genes defining ALCL cell state and dependencies, we here characterize super-enhancer regions by genome-wide H3K27ac ChIP-seq. In addition to known ALCL key regulators, the AP-1-member BATF3 and IL-2 receptor (IL2R)-components are among the top hits. Specific and high-level IL2R expression in ALCL correlates with BATF3 expression. Confirming a regulatory link, IL-2R-expression decreases following BATF3 knockout, and …

Rapid 3d Reconstruction Guided Embolization For Catastrophic Bleeding Following Vacuum Assisted Breast Biopsy; A Case Report And Review Of The Literature, Martin Halicek, Chenghao Qian, Driss Raissi, Xiaoqin Wang, Yevgen Chornenkyy, William B. Bates, Michael Winkler

Radiology Faculty Publications

The most clinically significant complication associated with stereotactic core needle biopsy of the breast is hematoma formation, which only occurs in less than 1% of biopsies and may require treatment. Cases of uncontrollable bleeding, refractory to repeated compression, resulting from biopsy are exceedingly rare. We present a case of catastrophic, uncontrollable bleeding and large hematoma formation resulting from stereotactic vacuum-assisted breast biopsy of a breast mass identified in screening mammography. Percutaneous embolization was planned and guided using 3D reconstructions from computed tomographic angiography, and bleeding was successfully controlled with micro-coil embolization.

Nsg-Pro Mouse Model For Uncovering Resistance Mechanisms And Unique Vulnerabilities In Human Luminal Breast Cancers, Yunguang Sun, Ning Yang, Fransiscus E Utama, Sameer S Udhane, Junling Zhang, Amy R Peck, Alicia Yanac, Katherine Duffey, John F Langenheim, Vindhya Udhane, Guanjun Xia, Jess F Peterson, Julie M Jorns, Marja T Nevalainen, Romain Rouet, Peter Schofield, Daniel Christ, Christopher J Ormandy, Anne Rosenberg, I Chervoneva, Shirng-Wern Tsaih, Michael J Flister, Serge Y Fuchs, Kay-Uwe Wagner, Hallgeir Rui

Department of Surgery Faculty Papers

Most breast cancer deaths are caused by estrogen receptor-α-positive (ER+) disease. Preclinical progress is hampered by a shortage of therapy-naïve ER+ tumor models that recapitulate metastatic progression and clinically relevant therapy resistance. Human prolactin (hPRL) is a risk factor for primary and metastatic ER+ breast cancer. Because mouse prolactin fails to activate hPRL receptors, we developed a prolactin-humanized Nod-SCID-IL2Rγ (NSG) mouse (NSG-Pro) with physiological hPRL levels. Here, we show that NSG-Pro mice facilitate establishment of therapy-naïve, estrogen-dependent PDX tumors that progress to lethal metastatic disease. Preclinical trials provide first-in-mouse efficacy of pharmacological hPRL suppression on residual ER+ human breast cancer …

Analysis Of Genes (Tmem106b, Grn, Abcc9, Kcnmb2, And Apoe) Implicated In Risk For Late-Nc And Hippocampal Sclerosis Provides Pathogenetic Insights: A Retrospective Genetic Association Study, Adam J. Dugan, Peter T. Nelson, Yuriko Katsumata, Lincoln M. P. Shade, Kevin L. Boehme, Merilee A. Teylan, Matthew D. Cykowski, Shubhabrata Mukherjee, John S. K. Kauwe, Timothy J. Hohman, Julie A. Schneider, Alzheimer’S Disease Genetics Consortium, David W. Fardo

Biostatistics Faculty Publications

Limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is the most prevalent subtype of TDP-43 proteinopathy, affecting up to 1/3rd of aged persons. LATE-NC often co-occurs with hippocampal sclerosis (HS) pathology. It is currently unknown why some individuals with LATE-NC develop HS while others do not, but genetics may play a role. Previous studies found associations between LATE-NC phenotypes and specific genes: TMEM106B, GRN, ABCC9, KCNMB2, and APOE. Data from research participants with genomic and autopsy measures from the National Alzheimer’s Coordinating Center (NACC; n = 631 subjects included) and the Religious Orders Study and Memory …